Participation of central GABAA receptors in the trigeminal processing of mechanical allodynia in rats

Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABAA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the IL-1β-induced mechanical allodynia. In the control group, application of GABA (100 µM) or muscimol (3 µM) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the IL-1β-treated rats. These results suggest that some large myelinated Aβ fibers gain access to the nociceptive system and elicit pain sensation via GABA(A) receptors under inflammatory pain conditions.

Anti-inflammatory, antiallodynic effects and quantitative analysis of gallic acid in spray dried powders from Phyllanthus niruri leaves, stems, roots and whole plant

The anti-inflammatory and antiallodynic effects of spray dried powders starting from leaves, stems, roots, the mixture of leaves and stems, as well as the whole plant aqueous solutions of Phyllanthus niruri L., Phyllanthaceae, were assessed. Gallic acid, used as chemical marker, was quantified by HPLC in the spray dried powders. Carrageenan-induced inflammatory and allodynic responses in the mouse paw were used as pharmacological models. Quantitative and qualitative differences among chemical composition of different herb parts were observed. The oral administration of leaves or leaves plus stems spray dried powders (100 mg/kg) significantly inhibited the carrageenan-induced allodynic effect (42 ± 5 and 54 ± 3%, respectively). Additionally, the spray dried powders of leaves significantly reduced carrageenan-induced paw oedema (35 ± 6%). The spray dried powders of roots, stems, or the mixture of leaves, stems and roots (100 mg/kg, p.o.) did not exhibit antiallodynic or antioedematogenic effect in the same model. In conclusion, differences in the chemical composition of spray dried powders from P. niruri are reflected in their in vivo pharmacological actions. Despite of a direct relationship of anti-inflammatory and antiallodynic effects with the gallic acid content had been observed, especially in the spray dried powders of leaves, the use of spray dried powders of leaves plus stems showed to be more effective, suggesting a synergic effect between their constituents.